Abstract
BackgroundThere is a need for novel treatment approaches in anorexia nervosa (AN). While there is broad knowledge with regard to altered appetite regulation and neuropsychological deficits in AN patients on the one hand, and the effects of estrogen replacement upon neuropsychological performance in healthy subjects on the other, up to now, no study has implemented estrogen replacement in AN patients, in order to examine its effects upon AN-associated and general psychopathology, neuropsychological performance and concentrations of peptide components of the hypothalamus-pituitary-adrenal (HPA) axis and within appetite-regulating circuits.MethodsThis is a randomized placebo-controlled clinical trial on the effects of a 10-week oral estrogen replacement (combination of ethinyl estradiol 0.03 mg and dienogest 2 mg) in adult female AN patients. The primary target is the assessment of the impact of sex hormone replacement upon neuropsychological performance by means of a neuropsychological test battery consisting of a test for verbal intelligence, the Trail making test A and B, a Go/No-go paradigm with food cues and the Wisconsin Card Sorting Test. Secondary targets include a) the examination of safety and tolerability (as mirrored by the number of adverse events), b) assessments of the impact upon eating disorder-specific psychopathology by means of the Eating Disorder Examination Questionnaire (EDE-Q) and the Eating Disorder Inventory-2 (EDI-2), c) the influence upon anxiety using the State-Trait-Anxiety Inventory (STAI), d) assessments of plasma cortisol levels during a dexamethasone-suppression test and appetite-regulating plasma peptides (ghrelin, leptin, insulin, glucose) during an oral glucose tolerance test and, e) a possible impact upon the prescription of antidepressants.DiscussionThis is the first study of its kind. There are no evidence-based psychopharmacological options for the treatment of AN. Thus, the results of this clinical trial may have a relevant impact on future treatment regimens. Novel approaches are necessary to improve rates of AN symptom remission and increase the rapidity of treatment response. Identifying the underlying biological (e.g. neuroendocrinological) factors that maintain AN or may predict patient treatment response represent critical future research directions. Continued efforts to incorporate novel pharmacological aspects into treatments will increase access to evidence-based care and help reduce the burden of AN.Trial registrationEuropean Clinical Trials Database, EudraCT number 2015–004184-36, registered November 2015; ClinicalTrials.gov Identifier: NCT03172533, retrospectively registered May 2017.
Highlights
There is a need for novel treatment approaches in anorexia nervosa (AN)
Watson et al [12] performed a detailed review of randomized controlled trials (RCTs) in AN published between 1980 and 2011; the authors found that no treatment has been shown to be superior than the others, with results primarily focused on short-term findings
The secondary outcome measures following the 10week intervention are: a) incidence of treatment-emergent adverse events (AEs) mirrored by the number of AEs, b) changes in psychopathology (EDE-Q, EDI-2, State-Trait-Anxiety Inventory (STAI), PHQ-9, Eating Disorder Quality of Life (EDQOL)) mirrored by changes in sum scores, c) changes in cortisol mirrored by changes in plasma cortisol levels during a dexamethasone suppression test as well as changes in plasma concentrations of the appetite-regulating peptides ghrelin, leptin, insulin and glucose during an oral glucose tolerance test (OGTT) and d) changes in antidepressant medication mirrored by changes in their use
Summary
Design This prospective, randomized, double-blind, placebocontrolled, monocentre phase IIa clinical trial will compare outcomes for estrogen-progestin-treated and placebo-treated female AN patients upon a series of outcome parameters (see below) during inpatient ANspecific psychotherapy. Following the treatment effects found in Misra et al [97], n = 25 patients are needed in both groups in order to achieve a statistical power of at least 80% considering a two-sided t-test with the common significance level of 5%. The secondary outcome measures following the 10week intervention are: a) incidence of treatment-emergent adverse events (AEs) (safety/tolerability) mirrored by the number of AEs (including AEs, adverse reactions [ARs], serious AEs, serious ARs and suspected unexpected serious ARs [SUSARs]), b) changes in psychopathology (EDE-Q, EDI-2, STAI, PHQ-9, EDQOL) mirrored by changes in sum scores, c) changes in cortisol mirrored by changes in plasma cortisol levels during a dexamethasone suppression test as well as changes in plasma concentrations of the appetite-regulating peptides ghrelin, leptin, insulin and glucose during an OGTT and d) changes in antidepressant medication mirrored by changes in their use
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